Tolerability benefits with sunitinib schedule switch

Sep 17 2015

By Lucy Piper, Senior medwireNews Reporter

Switching sunitinib treatment from a 4/2 to a modified 2/1 schedule can improve the tolerability profile for patients with metastatic renal cell carcinoma (mRCC), say researchers.

Such a switch resulted in a significant decrease in overall grade 3 to 4 toxicities and reduced the incidence of drug-specific toxicities such as fatigue, hypertension, hand–foot syndrome and thrombocytopenia.

The researchers note in the Annals of Oncology that the improved safety profile with a 2/1 schedule – 2 weeks on treatment followed by 1 week off – also meant that a potentially negative dose reduction was avoided in a large proportion of patients. All this without seeming to decrease efficacy, they add.

The study participants comprised 208 mRCC patients who started sunitinib treatment on the 4/2 schedule and thereafter switched to the 2/1 schedule due to toxicities, the most frequent of which was fatigue, and 41 patients who started sunitinib on the 2/1 schedule because of suboptimal clinical conditions. These two groups were compared with an external cohort of 211 patients treated solely with the 4/2 schedule.

Among the patients who switched from a 4/2 to 2/1 schedule, the overall incidence of toxicities of grade 3 or above fell significantly, from 45.7% to 8.2%. The benefit was comparable for 106 patients who were started and maintained on the full 50 mg dose of sunitinib following switching, for whom the incidence of toxicities fell from 41.5% to 6.6%.

Grade 3 to 4 drug-related adverse events were also reduced significantly as a result of the switch; specifically, fatigue (10.1 to 0%), hypertension (9.1 to 2.4%), hand–foot syndrome (10.1 to 3.4%) and thrombocytopenia (7.7 to 0.5%).

For the patients who started on a 2/1 schedule, the incidence of grade 3 or above adverse events was 26.8%, which did not differ significantly from the 29.4% incidence for the external 4/2 group of patients.

Although safety was the primary endpoint, lead researcher Sergio Bracarda (Ospedale San Donato, Arezzo, Italy) and team also analysed efficacy outcomes.

They found that patients switched to a 2/1 schedule had a progression-free survival (PFS) of 30.2 months, compared with 10.4 months in the 2/1 group and 9.7 months in the 4/2 group. And after adjustment for International mRCC Database Consortium criteria, the rates of 36-month PFS were 45.5%, 16.9% and 6.9%, respectively, and for overall survival 74.1%, 39.4% and 39.5%.

The team believes the findings could lead to more personalised RCC treatment. A strategy whereby patients who experience unmanageable toxicities with the 4/2 schedule are first switched to a better tolerated 2/1 schedule and then have their dose reduced eventually if necessary “widens the options for an individualization of sunitinib treatment, possibly delaying the initiation of a second-line therapy in nonprogressing patients with a poor tolerability”, they conclude

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